The major overall goals of this Program Project Grant, "Dendritic Cell Biology and Therapy" is to coordinately explore the major unsolved issue of modern cellular immunology, i.e. the difference in parameters allowing induction of tolerance or immunity to defined antigens. It is the central precept of this grant that progress in application of dendritic cells to the treatment of important human disease will best be realized by a coordinated approach engaging scientists studying cancer, transplantation and autoimmunity. It has long been appreciated that dendritic cells are specialized presenting cells (APC) with a unique ability to prime effective immune responses, and that this may give them a special importance in several human disease states known to have an immunological basis. All along, while great strides were being made in the understanding of the role of specific T cells and antibodies in mediating allergy, autoimmunity, graft rejection, or tumor immunity, it was also clear that these effectors represented the end stage of an immune response, the outcome of which was likely determined at its very initiation by the type of APC and the cytokine conditions under which the antigen was first presented. As is usually the case in science, testing of ideas must await development of new techniques and reagents, which are now available to study DC's. We envision 5 Projects and 4 Cores in the revised applications as listed below: I. Mechanism of Dendritic Cell-Based Tumor Immunization. Louis A. Falo and Michael T. Lotze. II. Dendritic Cell Mediated Therapy of Auto Immune Diabetes. Penelope Morel, Angus W. Thomson, Hideaki Tahara. III. Dendritic Cell Modulation of Autoreactive T- Lymphocytes. Timothy Wright, Susan McCarthy IV. Dendritic Cell Therapies Elicit Effective Anti-tumor Responses. Michael T. Lotze, Joseph Baar, Walter Storkus, Louis Falo, Andrew Amoscato. A. Administrative ore. Michael T. Lotze and Olivera J. Finn. B. Immunologic Monitoring and Diagnostic Laboratories . Theresa Whiteside, Elaine Elder. C. Imaging Core, Simon Watkins, Ronald Jaffe. D. Vector Core, Paul Robbins, Leaf Huang, Hideaki Tahara.